The long-term goal is to understand the initial stages of vision in normal humans, as well as their alteration by diseases of the retinal pigment epithelium (RPE) and outer retina. To achieve this, optical measurements will be used to study the initial stages of human vision: the in vivo capture and absorption of light energy by human cones. The ability of the cones to collect and guide light is controlled by their diameter, shape, and the difference in the index of refraction between the photoreceptors and the extracellular matrix. In contrast, the ability of the cones to absorb light is controlled by the amount of the photopigment in the outer segment, and the ability of the cones to guide the photons within the outer segments. To elucidate the interaction between cone structure and light capture, the variation in cone waveguide properties will be investigated with changes in wavelength, retinal location, and age. These measurements will be compared to in vivo measurements of cone spacing made using speckle interferometry. Changes in light collection and guiding functions should indicate severe pathology, including death of significant numbers of adjacent photoreceptors. The changes in the physical properties of the cones of patients with age-related macular degeneraion (AMD) will be examined to determine when and what sort of changes to the photoreceptors occur before vision is lost. These changes will be measured using photoreceptor alignment reflectometry. The alignment of the cones towards the pupil is an active process, yet the stimulus for alignment is not known. The variation in optical quality of the eyes' optics across the pupil will be compared with the alignment of the cones to test the hypothesis that the cones align towards the pupil to maximize the optical quality of the image. It will be tested whether the realignment of cones after resolution of retinal problems is guided by the optical quality of the eye. Maintaining the full complement of photopigment in the cones is an active process, requiring the function of the cones, the retinal pigment epithelium, and the flow of nutrients from the choroid. All of these are impacted by aging and also by AMD. Using low coherence interferometry, the in vivo bleaching and regeneration kinetics of the photopigments will be measured. This should facilitate understanding not only normal bleaching and regeneration, but also what goes wrong in retinal disease and eventually, whether it can be reversed by treatment.